Reproductive hormones

What is a hormone?

Definition of hormone

• Hormone– Greek “I excite” or “I arouse”

• First used by Starling in 1895

– Classical definition• Chemical signals that travel via bloodstream to

affect the function of the distant organ– Regulatory factor

• Secretory organ• Target organ/tissue

Definition of hormone

• Hormones– Contemporary definition

• Much broader• Local factors (produced and used without being

carried in the bloodstream)– Autocrine (produced and used by the same cell/tissue)– Paracrine (produced by the neighboring cells and

transported via the interstitial fluid)

LH FSH

Estradiol

Hypothalamus

Pituitarygland

GnRH

Ovary

Antrum

Granulosa cells

Theca internaTheca externa

Basementmembrane

Oocyte

Granulosa cells (GC) Theca

cells (TC)

Basement membrane

Classes of hormones

• Three general classes– Lipids

• Cholesterol derivatives (steroids)• 12-C fatty acid derivatives (eicosanoids)

– Proteins and polypeptides– Monoamines

Cholesterol and its derivatives

• Cholesterol– Large molecule

• Hydrocarbon ring

– Highly hydrophobic– Source

• Diet• De Novo synthesis

– Found in cell membrane

Cholesterol and its derivatives

• Derivatives– Vitamin D– Bile acid

• Lipid digestion

– Steroid hormones• Sex steroids• Adrenal steroild

– All cholesterol derivatives contain sterol ring

Steroid hormones

• Commonly called sex steroid hormones– Produced mainly by the gonads

• Ovaries and testis• Some production by placenta, adrenal gland, and

brain

– Water-insoluble but lipid soluble• Easily move across the plasma membrane• Bound to Steroid hormone-binging globulin during

transport

• Three classes of sex steroid hormones– Progestin/progestagens– Estrogens– Androgens

• Produced through metabolic process– Steroidogenesis

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Steroidogenesis

• Source of cholesterol– Acetate

• De Novo Synthesis

– Lipoproteins• HDL (humans and rodents)• LDL (cattle)

• Common pathway– Conversion of cholesterol to pregnenolone

• Splits into two different pathway with the same outcome– Delta-4 pathway

• Conversion of pregnenolone to progesterone• Conversion of progesterone to androstenedione

– Delta-5 pathway• Conversion of pregnenolone to androstenedione

• Production of estrogens– Final destination of steroidogenesis in the

ovary• Conversion of androgens (testosterone) to

estradiol-17 beta

– Some species (i.e. rats) use delta-4 pathway, whereas others (i.e. cows) prefer delta-5 pathway

General function of steroid hormones

• Development of physical characteristics– Male and female sex characteristics

• Primary (reproductive organs)• Secondary (physical)

• Reproductive success– Sexual behavior and libido– Fertility– Pregnancy

Eicosanoids

• Derivative of 12-C fatty acid (Arachidonic acid)– Prostaglandins (more important for reproduction)– Leukotriens

• Arachidonic acid released from phospholipid component of the cell membrane– Phospolipase A– Phospholipase C

• Prostaglandins– Produced from leukotriens through

cyclooxygenases– No specific organ of production

• Originally isolated from prostate gland• Many reproductive organs produce prostaglandins

– Quickly metabolized • Lungs

Protein hormones

• Three subclasses– Glycoproteins– Proteins

• Growth hormone• Prolactin• Placental lactogens

– Cytokines (immune system)– Polypeptdes

Glycoproteins

• Produced by the anterior pituitary– Gonadotropins

• Follicle-stimulating hormone (FSH)• Luteininzing hormone (LH)

– Thyroid-stimulating hormone (TSH)• Less important for regulation of gonadal function

• Produced by placenta– Chorionic gonadotropins (CG)

• Human (hCG)• Horse (eCG/PMSG)

• Structural similarity– Two subunits

• Alpha– Universal

• Beta– Unique to each hormone

• Linked together non-covalently (disulfide bridges)

– Glycosylated• Attachment of carbohydrate moiety onto the

subunits– Unique among hormones

Proteins

• Pituitary hormones– Growth hormone (GH)– Prolactin (PRL)

• Placental hormones– Unique to humans, rodents, and ruminants

• Placental lactogen (PL)• GH-Variant (GH-V)

• Affect metabolism and lactation• Affect ovarian functions

Cytokines

• Different from hormones– No specific organ/cells produce

• Immune response• Inflammation

– Multiple targets– Interactions to modulate activities of other

cytokines– Redundant functions– Auto/paracrine factor rather than endocrine

factor

• Ovarian proteins– Inhibins– Activins– Mullerian inhibitory substance/hormone (MIS)– Two subunits (alpha and beta)

• Different combination determines the nature of proteins

Polypeptides

• Small proteins– Short in length compared to proteins– Produced by cleaving large preprohormone

peptides

• Hypothalamic neuropeptides– Gonadotropin-

releasing hormone (GnRH)

• Regulates secretion of LH and FSH

• Composed of 10 amino acids

• Posterior pituitary hormones– Oxytocin

• Composed of 9 amino acids• Produced by the neurons within the hypothalamus

but secreted by the posterior pituitary gland• Induces contraction of smooth muscles• Critical for milk let-down